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Dosing Strategies and Patient Support in mCRC

Insights From: John L. Marshall, MD, MedStar Georgetown University Hospital; Tanios S. Bekaii-Saab, MD, Mayo Clinic
Published: Friday, Apr 05, 2019



Transcript: 

John L. Marshall, MD:
TAS-102, oral chemotherapy, cousin of 5-FU [fluorouracil], but not 5-FU. Not really responders, either, in this group.

Tanios S. Bekaii-Saab, MD: No responders.

John L. Marshall, MD: Being used in gastric in earlier lines in combination. So we’re seeing it being inserted in the combination regimens as chemotherapy.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: I’m hopeful that this will give us a new sort of fluoropyrimidine to play with through lines of therapy. You know we do 5-FU beyond progression all the time.

Tanios S. Bekaii-Saab, MD: All the time.

John L. Marshall, MD: And if we could show that switching it a little bit even helps, I think that would be positive.

Tanios S. Bekaii-Saab, MD: Theoretically, conceptually, this TAS-102 has an advantage over 5-FU in terms of protecting itself from some aspects that lead to the resistance of 5-FU. So theoretically you would think that it may have a slight edge over 5-FU. Not a significant edge, but a slight edge. But who knows how that edge will work when you start combining it with synergistic agents or other. It may also be more effective as a maintenance strategy on its own. There was this study in colorectal cancer, refractory, or elderly colorectal cancer patients with TAS-102 versus CAPE [capecitabine] plus BEV [bevacizumab], that actually showed an edge for TAS-102 plus BEV. Now, again, it needs to be reproduced. There’s a lot work that still needs to be done, but it was intriguing to see actually that there was a significant improvement from TAS-102 versus capecitabine.

John L. Marshall, MD: It also has its dosing problems too.

Tanios S. Bekaii-Saab, MD: It does.

John L. Marshall, MD: I’ve sort of drunk the Kool-Aid around optimizing the dose here too, but the pain of it is it’s 2 pill sizes. So in our system that’s 2 prescriptions. I can’t write that 1 script in my world. And then making sure that the patient understands that it’s 2 of these and 1 of these, etcetera.

Tanios S. Bekaii-Saab, MD: It can get confusing to patients.

John L. Marshall, MD: It can and so it really requires a lot of nursing support. The other piece there is the 2-week-on, 2-week-off schedule. And I have to say, a little slippery slope here is that if I get somebody with myelosuppression coming in for cycle 2, I’m pretty quick to go to an every-other-week kind of schedule. Do you think I’m wrong? What do you think?

Tanios S. Bekaii-Saab, MD: No. I think that ultimately; our experience with capecitabine was similar. We have the challenges of 2 weeks on, 1 week off. The challenges of 2 different dosages. In fact, literally, I can’t recall the last time I prescribed 150 mg for capecitabine. It’s 500; either go down, or go up.

John L. Marshall, MD: Go down or up, yes.

Tanios S. Bekaii-Saab, MD: Or go a little bit up if the patient’s younger. Never, you know it’s 2 or 3 pills or 4 pills, that’s the whole discussion. Simplifying is great. And I don’t think it affects outcome at the end of the day. We have no idea how we got to the dosages the way they did. All we know is that on the long run these patients do well and do really well, and you really don’t have to punish them. So with TAS-102 I think an every-other week regimen makes sense. I mean, what is….

John L. Marshall, MD: There’s no pharmacologic advantage that I can think about.

Tanios S. Bekaii-Saab, MD: Absolutely not. Think about it like this. All our fluoropyrimidines, at least the 5-FU; the 5-FU given every other week, over 48 hours, and it’s not even the whole week, it’s 2 days every 2 weeks, seems to do better than a bolus 5-FU. It seems to do equally well with much less toxicities than the continuous infusion.

John L. Marshall, MD: Which is about the same as oral.

Tanios S. Bekaii-Saab, MD: Exactly. So we know you don’t need that constant pressure and then let go. I think a better measured approach would be exactly likely you’re doing—every other week. And then I think the next question would be, do you really need those 2 different, can we change the dosage and can we just simplify it to just 1 rather than 2? And the elderly patients, they forget to take their diabetes pill, their blood pressure pill. You think they’re going to handle all this? It’s tough, it’s tough. I’m not even sure that they comply well with it.

John L. Marshall, MD: TAS-102, oral chemotherapy, cousin of 5-FU [fluorouracil], but not 5-FU. Not really responders, either, in this group.

Tanios S. Bekaii-Saab, MD: No responders.

John L. Marshall, MD: Being used in gastric in earlier lines in combination. So we’re seeing it being inserted in the combination regimens as chemotherapy.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: I’m hopeful that this will give us a new sort of fluoropyrimidine to play with through lines of therapy. You know we do 5-FU beyond progression all the time.

Tanios S. Bekaii-Saab, MD: All the time.

John L. Marshall, MD: And if we could show that switching it a little bit even helps, I think that would be positive.

Tanios S. Bekaii-Saab, MD: Theoretically, conceptually, this TAS-102 has an advantage over 5-FU in terms of protecting itself from some aspects that lead to the resistance of 5-FU. So theoretically you would think that it may have a slight edge over 5-FU. Not a significant edge, but a slight edge. But who knows how that edge will work when you start combining it with synergistic agents or other. It may also be more effective as a maintenance strategy on its own. There was this study in colorectal cancer, refractory, or elderly colorectal cancer patients with TAS-102 versus CAPE [capecitabine] plus BEV [bevacizumab], that actually showed an edge for TAS-102 plus BEV. Now, again, it needs to be reproduced. There’s a lot work that still needs to be done, but it was intriguing to see actually that there was a significant improvement from TAS-102 versus capecitabine.

John L. Marshall, MD: It also has its dosing problems too.

Tanios S. Bekaii-Saab, MD: It does.

John L. Marshall, MD: I’ve sort of drunk the Kool-Aid around optimizing the dose here too, but the pain of it is it’s 2 pill sizes. So in our system that’s 2 prescriptions. I can’t write that 1 script in my world. And then making sure that the patient understands that it’s 2 of these and 1 of these, etcetera.

Tanios S. Bekaii-Saab, MD: It can get confusing to patients.

John L. Marshall, MD: It can and so it really requires a lot of nursing support. The other piece there is the 2-week-on, 2-week-off schedule. And I have to say, a little slippery slope here is that if I get somebody with myelosuppression coming in for cycle 2, I’m pretty quick to go to an every-other-week kind of schedule. Do you think I’m wrong? What do you think?

Tanios S. Bekaii-Saab, MD: No. I think that ultimately; our experience with capecitabine was similar. We have the challenges of 2 weeks on, 1 week off. The challenges of 2 different dosages. In fact, literally, I can’t recall the last time I prescribed 150 mg for capecitabine. It’s 500; either go down, or go up.

John L. Marshall, MD: Go down or up, yes.

Tanios S. Bekaii-Saab, MD: Or go a little bit up if the patient’s younger. Never, you know it’s 2 or 3 pills or 4 pills, that’s the whole discussion. Simplifying is great. And I don’t think it affects outcome at the end of the day. We have no idea how we got to the dosages the way they did. All we know is that on the long run these patients do well and do really well, and you really don’t have to punish them. So with TAS-102 I think an every-other week regimen makes sense. I mean, what is….

John L. Marshall, MD: There’s no pharmacologic advantage that I can think about.

Tanios S. Bekaii-Saab, MD: Absolutely not. Think about it like this. All our fluoropyrimidines, at least the 5-FU; the 5-FU given every other week, over 48 hours, and it’s not even the whole week, it’s 2 days every 2 weeks, seems to do better than a bolus 5-FU. It seems to do equally well with much less toxicities than the continuous infusion.

John L. Marshall, MD: Which is about the same as oral.

Tanios S. Bekaii-Saab, MD: Exactly. So we know you don’t need that constant pressure and then let go. I think a better measured approach would be exactly likely you’re doing—every other week. And then I think the next question would be, do you really need those 2 different, can we change the dosage and can we just simplify it to just 1 rather than 2? And the elderly patients, they forget to take their diabetes pill, their blood pressure pill. You think they’re going to handle all this? It’s tough, it’s tough. I’m not even sure that they comply well with it.


Transcript Edited for Clarity
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Transcript: 

John L. Marshall, MD:
TAS-102, oral chemotherapy, cousin of 5-FU [fluorouracil], but not 5-FU. Not really responders, either, in this group.

Tanios S. Bekaii-Saab, MD: No responders.

John L. Marshall, MD: Being used in gastric in earlier lines in combination. So we’re seeing it being inserted in the combination regimens as chemotherapy.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: I’m hopeful that this will give us a new sort of fluoropyrimidine to play with through lines of therapy. You know we do 5-FU beyond progression all the time.

Tanios S. Bekaii-Saab, MD: All the time.

John L. Marshall, MD: And if we could show that switching it a little bit even helps, I think that would be positive.

Tanios S. Bekaii-Saab, MD: Theoretically, conceptually, this TAS-102 has an advantage over 5-FU in terms of protecting itself from some aspects that lead to the resistance of 5-FU. So theoretically you would think that it may have a slight edge over 5-FU. Not a significant edge, but a slight edge. But who knows how that edge will work when you start combining it with synergistic agents or other. It may also be more effective as a maintenance strategy on its own. There was this study in colorectal cancer, refractory, or elderly colorectal cancer patients with TAS-102 versus CAPE [capecitabine] plus BEV [bevacizumab], that actually showed an edge for TAS-102 plus BEV. Now, again, it needs to be reproduced. There’s a lot work that still needs to be done, but it was intriguing to see actually that there was a significant improvement from TAS-102 versus capecitabine.

John L. Marshall, MD: It also has its dosing problems too.

Tanios S. Bekaii-Saab, MD: It does.

John L. Marshall, MD: I’ve sort of drunk the Kool-Aid around optimizing the dose here too, but the pain of it is it’s 2 pill sizes. So in our system that’s 2 prescriptions. I can’t write that 1 script in my world. And then making sure that the patient understands that it’s 2 of these and 1 of these, etcetera.

Tanios S. Bekaii-Saab, MD: It can get confusing to patients.

John L. Marshall, MD: It can and so it really requires a lot of nursing support. The other piece there is the 2-week-on, 2-week-off schedule. And I have to say, a little slippery slope here is that if I get somebody with myelosuppression coming in for cycle 2, I’m pretty quick to go to an every-other-week kind of schedule. Do you think I’m wrong? What do you think?

Tanios S. Bekaii-Saab, MD: No. I think that ultimately; our experience with capecitabine was similar. We have the challenges of 2 weeks on, 1 week off. The challenges of 2 different dosages. In fact, literally, I can’t recall the last time I prescribed 150 mg for capecitabine. It’s 500; either go down, or go up.

John L. Marshall, MD: Go down or up, yes.

Tanios S. Bekaii-Saab, MD: Or go a little bit up if the patient’s younger. Never, you know it’s 2 or 3 pills or 4 pills, that’s the whole discussion. Simplifying is great. And I don’t think it affects outcome at the end of the day. We have no idea how we got to the dosages the way they did. All we know is that on the long run these patients do well and do really well, and you really don’t have to punish them. So with TAS-102 I think an every-other week regimen makes sense. I mean, what is….

John L. Marshall, MD: There’s no pharmacologic advantage that I can think about.

Tanios S. Bekaii-Saab, MD: Absolutely not. Think about it like this. All our fluoropyrimidines, at least the 5-FU; the 5-FU given every other week, over 48 hours, and it’s not even the whole week, it’s 2 days every 2 weeks, seems to do better than a bolus 5-FU. It seems to do equally well with much less toxicities than the continuous infusion.

John L. Marshall, MD: Which is about the same as oral.

Tanios S. Bekaii-Saab, MD: Exactly. So we know you don’t need that constant pressure and then let go. I think a better measured approach would be exactly likely you’re doing—every other week. And then I think the next question would be, do you really need those 2 different, can we change the dosage and can we just simplify it to just 1 rather than 2? And the elderly patients, they forget to take their diabetes pill, their blood pressure pill. You think they’re going to handle all this? It’s tough, it’s tough. I’m not even sure that they comply well with it.

John L. Marshall, MD: TAS-102, oral chemotherapy, cousin of 5-FU [fluorouracil], but not 5-FU. Not really responders, either, in this group.

Tanios S. Bekaii-Saab, MD: No responders.

John L. Marshall, MD: Being used in gastric in earlier lines in combination. So we’re seeing it being inserted in the combination regimens as chemotherapy.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: I’m hopeful that this will give us a new sort of fluoropyrimidine to play with through lines of therapy. You know we do 5-FU beyond progression all the time.

Tanios S. Bekaii-Saab, MD: All the time.

John L. Marshall, MD: And if we could show that switching it a little bit even helps, I think that would be positive.

Tanios S. Bekaii-Saab, MD: Theoretically, conceptually, this TAS-102 has an advantage over 5-FU in terms of protecting itself from some aspects that lead to the resistance of 5-FU. So theoretically you would think that it may have a slight edge over 5-FU. Not a significant edge, but a slight edge. But who knows how that edge will work when you start combining it with synergistic agents or other. It may also be more effective as a maintenance strategy on its own. There was this study in colorectal cancer, refractory, or elderly colorectal cancer patients with TAS-102 versus CAPE [capecitabine] plus BEV [bevacizumab], that actually showed an edge for TAS-102 plus BEV. Now, again, it needs to be reproduced. There’s a lot work that still needs to be done, but it was intriguing to see actually that there was a significant improvement from TAS-102 versus capecitabine.

John L. Marshall, MD: It also has its dosing problems too.

Tanios S. Bekaii-Saab, MD: It does.

John L. Marshall, MD: I’ve sort of drunk the Kool-Aid around optimizing the dose here too, but the pain of it is it’s 2 pill sizes. So in our system that’s 2 prescriptions. I can’t write that 1 script in my world. And then making sure that the patient understands that it’s 2 of these and 1 of these, etcetera.

Tanios S. Bekaii-Saab, MD: It can get confusing to patients.

John L. Marshall, MD: It can and so it really requires a lot of nursing support. The other piece there is the 2-week-on, 2-week-off schedule. And I have to say, a little slippery slope here is that if I get somebody with myelosuppression coming in for cycle 2, I’m pretty quick to go to an every-other-week kind of schedule. Do you think I’m wrong? What do you think?

Tanios S. Bekaii-Saab, MD: No. I think that ultimately; our experience with capecitabine was similar. We have the challenges of 2 weeks on, 1 week off. The challenges of 2 different dosages. In fact, literally, I can’t recall the last time I prescribed 150 mg for capecitabine. It’s 500; either go down, or go up.

John L. Marshall, MD: Go down or up, yes.

Tanios S. Bekaii-Saab, MD: Or go a little bit up if the patient’s younger. Never, you know it’s 2 or 3 pills or 4 pills, that’s the whole discussion. Simplifying is great. And I don’t think it affects outcome at the end of the day. We have no idea how we got to the dosages the way they did. All we know is that on the long run these patients do well and do really well, and you really don’t have to punish them. So with TAS-102 I think an every-other week regimen makes sense. I mean, what is….

John L. Marshall, MD: There’s no pharmacologic advantage that I can think about.

Tanios S. Bekaii-Saab, MD: Absolutely not. Think about it like this. All our fluoropyrimidines, at least the 5-FU; the 5-FU given every other week, over 48 hours, and it’s not even the whole week, it’s 2 days every 2 weeks, seems to do better than a bolus 5-FU. It seems to do equally well with much less toxicities than the continuous infusion.

John L. Marshall, MD: Which is about the same as oral.

Tanios S. Bekaii-Saab, MD: Exactly. So we know you don’t need that constant pressure and then let go. I think a better measured approach would be exactly likely you’re doing—every other week. And then I think the next question would be, do you really need those 2 different, can we change the dosage and can we just simplify it to just 1 rather than 2? And the elderly patients, they forget to take their diabetes pill, their blood pressure pill. You think they’re going to handle all this? It’s tough, it’s tough. I’m not even sure that they comply well with it.


Transcript Edited for Clarity
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